CLINICAL MEDICAL POLICY Fetal Aneuploidy Testing Using Noninvasive Cell-Free Fetal Policy Name: DNA Policy Number: MP-003-MD-DE Responsible Department(s): Medical Management Provider Notice Date: 08/15/2019; 10/15/2018; 10/01/2017 Issue Date: 09/16/2019; 11/15/2018 Original Effective Date: 09/16/2019; 11/15/2018; 11/01/2017 Annual Approval Date: 07/16/2020 Revision Date: 07/16/2019; 09/11/2018; 08/09/2017 Products: Highmark Health Options Medicaid Application: All participating hospitals and providers Page Number(s): 1 of 10

DISCLAIMER

Highmark Health Options medical policy is intended to serve only as a general reference resource regarding coverage for the services described. This policy does not constitute medical advice and is not intended to govern or otherwise influence medical decisions.

POLICY STATEMENT

Highmark Health Options provides coverage for laboratory benefit under the medical benefits of the Company’s Medicaid products for medically necessary, noninvasive, circulating cell-free DNA prenatal testing of fetal aneuploidy as screening tools for trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome) or trisomy 13 (Patau syndrome). Circulating cell-free fetal DNA crosses the placenta and can be isolated in maternal plasma.

This policy is designed to address medical necessity guidelines that are appropriate for the majority of individuals with a particular disease, illness or condition. Each person’s unique clinical circumstances warrant individual consideration, based upon review of applicable medical records.

The qualifications of the policy will meet the standards of the National Committee for Quality Assurance (NCQA) and the Delaware Department of Health and Social Services (DHSS) and all applicable state and federal regulations.

Policy No. MP-003-MD-DE Page 1 of 10 DEFINITIONS

Aneuploidy – An abnormal number of chromosomes in the cell.

Trisomy 13 – A rare condition associated with more severe structural malformations than trisomy 21 or 18. Patau syndrome is an example of trisomy of chromosome 13.

Trisomy 18 – The second most common autosomal trisomy detected in the second trimester. This condition is almost always lethal in early childhood. Edwards syndrome is an example of trisomy of chromosome 18.

Trisomy 21 – The most common single cause of birth defects. Down syndrome is an example of trisomy of chromosome 21.

PROCEDURES

1. The following tests are commercially available: A. Harmony™ Prenatal Test B. MaterniT21™ Plus C. verifi® Prenatal Test D. Panorama E. informaSeq℠ F. QNatal™ Advanced

2. These tests are considered eligible as advanced screening technology for pregnant women at high risk, as determined by any of the following: A. The patient underwent genetic pretest counseling in order to inform persons being tested about the advantages and limitations of the test as applied to a unique person; AND B. The current pregnancy is not a multiple gestation; AND C. Advanced maternal age (pregnant women aged 35 years and older at expected time of delivery); OR D. Testing is offered anytime from 10 weeks gestational age on through the duration of pregnancy in women with singleton gestation; OR E. Fetal ultrasonography findings predictive of increased risk of fetal aneuploidy (i.e., absent or hypoplastic nasal bone, choroid plexus cyst, echogenic bowel, echogenic intracardiac focus, fetal pyelectasis, nuchal translucency, nuchal fold, ventriculomegaly, and shortened femur or humerus); OR F. Positive screening test for an aneuploidy, including first trimester, sequential, or integrated screen, or a positive quadruple screen; OR G. History of a prior maternal pregnancy with an aneuploidy; OR H. Parental balanced Robertsonian translocation with increased risk for fetal trisomy 13 or trisomy 21; OR A. Noninvasive prenatal testing using the cell-free DNA test for trisomies 21, 18, and 13 is to be used in pregnant women at increased risk in lieu of amniocentesis; AND

3. When Noninvasive Cell-Free Fetal DNA is not covered A. Services for DNA-based noninvasive tests of fetal aneuploidy in pregnant women who do not meet

Policy No. MP-003-MD-DE Page 2 of 10 the above criteria or in women who are pregnant with multiple gestations are unproven; therefore investigational; OR B. Services for DNA-based prenatal microdeletion and micro-duplication syndromes are unproven; therefore investigational; OR C. Use of noninvasive prenatal testing using the cell-free DNA test for the determination of fetal sex or fetal RHD genotyping is not medically necessary and will require case-by-case review; OR D. Women with positive cell free DNA tests should be offered invasive prenatal diagnostic testing(amniocentesis or chorionic villus sampling) and detailed counseling

4. Post-payment Audit Statement The medical record must include documentation that reflects the medical necessity criteria and is subject to audit by Highmark Health Options at any time pursuant to the terms of your provider agreement.

5. Genetic Counseling Pre- and post-test genetic counseling is required to be performed by an independent (not employed by a genetic testing lab) genetic provider prior to genetic counseling for mutations. This service is necessary in order to inform persons being tested about the benefits and limitations of a specific genetic test for the specific patient. Genetic testing for mutation requires documentation of medical necessity from one of the following providers who has evaluated the patient and intends to see the person after testing has been performed for counseling: A. Board Eligible or Board Certified Genetic Counselor B. Advanced Genetics Nurse C. Genetic Clinical Nurse D. Advanced Practice Nurse in Genetics E. Board Eligible or Board Certified Clinical Geneticist F. A physician or other obstetrical provider specializing for the indications(s) for genetic testing

6. Place of Service The place of service for testing to be administered is outpatient.

GOVERNING BODIES APPROVAL

The cell-free DNA tests are laboratory developed tests that do not require premarket approval by the FDA. These types of tests are regulated by the Centers for Medicare & Medicaid as part of the Clinical Laboratory Improvement Amendments of 1988 (CLIA). The regulations of the CLIA Amendments do not include validation of specific tests but rather that there is procedural compliance. Commercially available tests include but are not limited to the following:  Sequenom MaterniT21™ PLUS test: Tests for trisomy 21, 18, and 13 and fetal sex aneuploidies. Their enhanced sequencing series includes testing for trisomies 16 and 22 and 7 microdeletions: 22q deletion syndrome (DiGeorge syndrome), 5p (cri du chat syndrome), 15q (Prader-Willi and Angelman syndromes), 1p36 deletion syndrome, 4p (Wolf-Hirschhorn syndrome), 8q (Langer- Giedion syndrome), and 11q (Jacobsen syndrome). The test uses massive parallel sequencing (MPS) and reports results as positive or negative. The enhanced sequencing series is offered on an opt-out basis.  Harmony™ Prenatal test: (Ariosa was acquired by Roche in January 2015). Tests for trisomies 21, 18, and 13. Uses directed DNA analysis, results reported as risk score.  Natera Panorama™ prenatal test: Tests for detecting trisomy 21, 18, and 13, as well as select sex

Policy No. MP-003-MD-DE Page 3 of 10 chromosome abnormalities. Uses single-nucleotide polymorphisms technology; results reported as risk score. An extended panel tests for 5 microdeletions: 22q deletion syndrome (DiGeorge syndrome), 5p (cri du chat syndrome), 15q11-13 (Prader-Willi and Angelman syndromes), and 1p36 deletion syndrome. Screening for 22q11.2 will be included in the panel unless the opt-out option is selected; screening for the remaining 4 microdeletions is offered on an opt-in basis.  Verifi® prenatal test: Tests for trisomy 21, 18, and 13 and fetal sex chromosome aneuploidies. The test uses MPS and calculates a normalized chromosomal value [NPS]; reports results as 1 of 3 categories: No Aneuploidy Detected, Aneuploidy Detected, or Aneuploidy Suspected.  InformaSeqSM prenatal test: Tests for detecting trisomy 21, 18, and 13, with optional additional testing for select sex chromosome abnormalities. Uses Illumina platform and reports results in similar manner.  QNatal™ Advanced (Quest Diagnostics): Tests for trisomies 21, 18, and 13.

Additional information is available online at: http://www.fda.gov/medicaldevices/deviceregulationandguidance/ivdregulatoryassistance/ucm124105. htm

CODING REQUIREMENTS

Procedure Codes CPT Description Codes 81420 Fetal chromosomal aneuploidy (e.g., trisomy 21, monosomy X) genomic sequence analysis panel, circulating cell-free fetal DNA in maternal blood, must include analysis of chromosomes 13.18. & 21 81507 Fetal aneuploidy (trisomy 21, 18, and 13) DNA sequence analysis of selected regions using maternal plasma, algorithm reported as a risk score for each trisomy 0009M Fetal aneuploidy (trisomy 21, and 18) DNA sequencing of selected regions using maternal plasma, algorithm reported as a risk score for each trisomy

*Non-covered Procedure Code CPT Code Description 81422 Fetal chromosomal microdeletions(s) genomic sequence analysis (e.g., DiGeorge syndrome, Cri-du-chat-syndrome), circulating cell-free DNA in maternal blood 0060U Twin zygosity, genomic target sequence analysis of chromosome 2, using circulating cell-free fetal DNA in maternal blood *All requests for this procedure must be referred to a Medical Director for approval.

Diagnosis Codes ICD-10 Description Codes O09.291 Supervision of pregnancy with other poor reproductive or obstetric history, first trimester O09.292 Supervision of pregnancy with other poor reproductive or obstetric history, second trimester O09.293 Supervision of pregnancy with other poor reproductive or obstetric history, third trimester O09.299 Supervision of pregnancy with other poor reproductive or obstetric history, unspecified trimester O09.511 Supervision of elderly primigravida, first trimester O09.512 Supervision of elderly primigravida, second trimester O09.513 Supervision of elderly primigravida, third trimester

Policy No. MP-003-MD-DE Page 4 of 10 O09.519 Supervision of elderly primigravida, unspecified trimester O09.521 Supervision of elderly multigravida, first trimester O09.522 Supervision of elderly multigravida, second trimester O09.523 Supervision of elderly multigravida, third trimester O09.529 Supervision of elderly multigravida, unspecified trimester O28.1 Abnormal hematological finding on antenatal screening of mother O28.2 Abnormal cytological finding on antenatal screening of mother O28.3 Abnormal ultrasonic finding on antenatal screening of mother O28.4 Abnormal radiological finding on antenatal screening of mother O28.5 Abnormal chromosomal and genetic finding on antenatal screening of mother O28.8 Other abnormal findings on antenatal screening of mother O28.9 Unspecified abnormal finding on antenatal screening of mother O35.0XX9 Maternal care for (suspected) chromosomal nervous system malformation in fetus, other fetus O35.1XX0 Maternal care for (suspected) chromosomal abnormality in fetus, not applicable or unspecified O35.1XX1 Maternal care for (suspected) chromosomal abnormality in fetus, fetus 1 O35.1XX9 Maternal care for (suspected) chromosomal abnormality in fetus, other fetus Q90.0 Trisomy 21, nonmosaicism (meiotic nondisjunction) Q90.1 Trisomy 21, mosaicism (mitotic nondisjunction) Q90.2 Trisomy 21, translocation Q90.9 Down syndrome, unspecified Q91.0 Trisomy 18, nonmosaicism (meiotic nondisjunction) Q91.1 Trisomy 18, mosaicism (mitotic nondisjunction) Q91.2 Trisomy 18, translocation Q91.3 Trisomy 18, unspecified Q91.4 Trisomy 13, nonmosaicism (meiotic nondisjunction) Q91.5 Trisomy 13, mosaicism (mitotic nondisjunction) Q91.6 Trisomy 13, translocation Q91.7 Trisomy 13, unspecified Q92.0 Whole chromosome trisomy, nonmosaicism (meiotic nondisjunction) Q92.1 Whole chromosome trisomy, mosaicism (mitotic nondisjunction) Q92.2 Partial trisomy Q92.5 Duplication with other complex rearrangements; partial trisomy due to unbalanced translocations Q92.61 Marker chromosomes in normal individual Q92.62 Marker chromosomes in abnormal individual Q92.7 Triploidy and polyploidy Q92.8 Other specified trisomies and partial trisomies of autosomes Q92.9 Trisomy and partial trisomy of autosomes, unspecified Q95.0 Balanced translocation and insertion in normal individual Q95.1 Chromosome inversion in normal individual Q95.2 Balanced autosomal rearrangement in abnormal individual Q95.3 Balanced sex/autosomal rearrangement in abnormal individual Q95.5 Individual with autosomal fragile site Q95.8 Other balanced rearrangements and structural markers Q95.9 Balanced rearrangement and structural marker, unspecified Z13.71 Encounter for nonprocreative screening for genetic disease carrier status Z13.79 Encounter for screening for other specified diseases and disorders Z31.438 Encounter for other genetic testing of female for procreative management

Policy No. MP-003-MD-DE Page 5 of 10 REIMBURSEMENT

Participating facilities will be reimbursed per their Highmark Health Options contract.

SUMMARY OF LITERATURE

Fetal chromosomal abnormalities occur in approximately 1 out of 160 live births (Lalani, 2017). There are many fetal chromosomal abnormalities that are aneuploidies. Aneuploidies are defined as an abnormal number of chromosomes and trisomy syndromes are aneuploidies involving 3 copies of 1 chromosome. Maternal age is the most important risk factor for trisomy syndromes, for instance the approximate risk for a trisomy 21 (T21; Down syndrome) of a fetus is 1 in 1100 affected births at age 25 to 29 (Hook, 1983). The approximate risk for trisomy 21 increases to 1 in 250 affected births at age 35 and to 1 in 75 at age 40 (Hook, 1983). In addition to T21, other trisomy syndromes include T18 (Edwards syndrome) and T13 (Patau Syndrome).

In 2015, the American College of Obstetricians and Gynecologists (ACOG) reported that noninvasive prenatal testing using cell-free fetal DNA from the plasma of pregnant women is an important screening tool for fetal aneuploidy. In addition, the ACOG society identified the following indications as appropriate for cell-free DNA:  Maternal age 35 years or older at time of delivery  Fetal ultra-sonographic findings predicting increased risk of fetal aneuploidy  History of prior pregnancy with aneuploidy; positive screening test for aneuploidy, including first trimester, sequential, or integrated screen, or a positive quadruple screen  Parental balanced Robertsonian translocation with increased risk for fetal trisomy 13 or trisomy 21

In May 2016, ACOG and the Society of Maternal-Fetal Medicine (SMFM) issued new guidelines for prenatal diagnostic and screening tests for genetic disorders. The new guidelines state that fetal aneuploidy testing using cell-free fetal DNA should be offered for any one of the following:  The patient is 35 years of age or older at delivery  Fetal ultrasound findings indicate an increased risk of aneuploidy  The patient has had a positive first- or second-trimester screening test results for aneuploidy  There is a parental balanced Robertsonian translocation with an increased risk of fetal trisomy 13 or trisomy 21.

Furthermore, the guidelines state that cell free DNA screening may be offered anytime from 10 weeks on through the duration of the pregnancy as it is the only screen available in the third trimester. This testing remains a screening test that can have false positives and false negatives. In the situation where no reportable results are available from a serum sample, because these unreportable results have shown to have a higher association with being true positives; unreportable results should be treated as a report of increased risk.

ACOG commented that cell-free DNA testing should not be offered to low-risk women or women with multiple gestations, or be part of routine prenatal laboratory testing because the test has not been evaluated in these groups.

Policy No. MP-003-MD-DE Page 6 of 10 In a nested case-controlled study, Bianchi et al. (2012), reported on the use of massively parallel DNA sequencing to detect fetal aneuploidy with 2,882 high-risk women. The study was termed the “MatErnal BLood IS Source to Accurately diagnose fetal aneuploidy (MELISSA).” These women were scheduled for amniocentesis or chorionic villus sampling at 60 different sites in the United States. The authors reported that 89 of 89 trisomy 18 cases were correctly identified (sensitivity 100%, 95% confidence interval 95.9 to 100), 35 of the 36 trisomy 18 were classified correctly, as were 11 of the 14 trisomy 13 cases and 15 of the 16 monosomy X cases. There were no false positive results for autosomal aneuploidies. However, it was noted that this was a nested case control study and did not represent true population prevalence. Further studies that included larger numbers of unaffected controls were recommended.

The Society for Maternal Fetal Medicine (2015) stated cell-free DNA screening is largely recommended in patients at higher risk for aneuploidy and not the lower risk populations since there is limited studies on this population. The Society for Maternal Fetal Medicine (SMFM) does not consider cell-free DNA screening as first-line screening and that conventional screening methods should be utilized in this group.

In the analysis performed by Norton and colleagues (2013), it was stated that the use of the cell-free DNA in maternal plasma represents a tremendous advance in prenatal diagnosis. In this analysis, it was noted that true cost-utility analysis is necessary to determine the actual clinical effectiveness of this screening in the general prenatal population.

Palomaki et al. (2011) noted that measurement of circulating cell-free DNA in maternal plasma resulted in a Down syndrome detection rate of 98.6% (209/212), a false-positive rate of 0.20% (3/1471), and the testing failed in 13 pregnancies (0.8%); all were euploid. Before unblinding, the primary testing laboratory also reported multiple alternative interpretations. Adjusting chromosome 21 counts for guanine cytosine base content had the largest impact on improving performance.

Langlois and colleagues (2013) provided an analysis of published studies on the use of cell-free DNA in maternal plasma for the noninvasive diagnosis of Down syndrome, trisomy 18, and trisomy 13. The authors reported the testing should be an available option to women at increased risk in lieu of amniocentesis. Use of cell-free fetal DNA testing in average-risk pregnancies is not supported as a replacement for the current maternal screening approach using biochemical serum markers with or without fetal nuchal translucency ultrasound.

Norton et al. (2015) published a large study evaluating cell-free DNA testing in a general population sample. The study included adult women with a singleton pregnancy undergoing routine first-trimester aneuploidy screening between 10.0 and 14.3 weeks of gestation. The patients underwent cell-free DNA testing and standard screening with maternal serum markers and nuchal translucency. In addition, the authors conducted a preplanned sub-analysis in ‘low-risk’ women defined as women younger than 35 years of age and women who had a risk of T21 of less than 1 in 270 on standard screening. There were a total of 15,841 participants, and chromosomal anomalies were identified in 68 cases. There were 83 with T21, 10 with T18, 6 with T13, and the remainder of cases had less common aneuploidies. The Area Under the Curve (AUC) for T21 was 0.999 for cell-free DNA testing and 0.958 for standard screening (p = 0.001). In the sub-analysis of the low-risk women, it was reported that cell-free DNA testing correctly identified 19 cases of T21, with six false positives. When low risk was defined as a risk less than 1 in 270 on standard screening, cell-free DNA testing identified all eight cases of T21 with six false positives.

Fetal chromosomal microdeletions in genomic sequence analysis are chromosomal deletions that are too small to be detected by microscopy or conventional cytogenetic methods. Microdeletions and microduplications are known as copy number variations (CNVs). There are several genomic disorders

Policy No. MP-003-MD-DE Page 7 of 10 associated with microdeletions such as DiGeorge syndrome and Cri-du-chat syndrome. These disorders may have distinctive and serious clinical features such as cardiac anomalies, immune deficiency, palatal defects, and developmental delay.

The clinical utility of microdeletion testing is unknown. At this time, there is no data on whether testing for microdeletions improves outcomes in comparison to the current standards of care. Additional clinical studies are needed to gain experience with routine genetic screening for microdeletions as well as clarity on clinical follow-up for detected microdeletions. The American College of Medical Genetics and Genomics (2016) does not recommend microdeletion screening. If this level of information is desired, then appropriate diagnostic testing (e.g., amniocentesis) is recommended.

POLICY SOURCE(S)

Ashoor G., Syngelaki A., Wagner M., et al. Chromosome-selective sequencing of maternal plasma cell- free DNA for first-trimester detection of trisomy 21 and trisomy 18. Am J Obstet Gynecol. 2012; 206(4):322.e1-5.

Palomaki G.E., Deciu C., Kloza E.M., et al. DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study. Genet Med. 2012; 14(3):296-305.

Sparks A.B., Struble C.A., Wang E.T., et al. Noninvasive prenatal detection and selective analysis of cell- free DNA obtained from maternal blood: evaluation for trisomy 21 and trisomy 18. Am J Obstet Gynecol. 2012; 206(4):319.e1-9.

Garfield S.S., Armstrong S.O. Clinical and cost consequences of incorporating a novel non-invasive prenatal test into the diagnostic pathway for fetal trisomies. Journal of Managed Care Medicine. 2012; 15(2):34-41.

Norton M.E., Brar H., Weiss J., et al. Non-Invasive Chromosomal Evaluation (NICE) study: results of a multicenter, prospective, cohort study for detection of fetal trisomy 21 and trisomy 18. Am J Obstet Gynecol. 2012 Aug; 207(2):137.e1-8.

Cell-free DNA screening for fetal aneuploidy. Committee Opinion No. 640. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2015; 126:e31-7. Accessed in January 21, 2016.

Palomaki G.E., Kloza E.M., Lambert-Messerlian G.M., et al. DNA sequencing of maternal plasma to detect Down syndrome: An international clinical validation study. Genetics in Medicine. 2011 Nov; 13(11):913-920.

Gil M.M., Quezada M.S., Bregant B., et al. Implementation of maternal blood cell-free DNA testing in early screening for aneuploidies. Ultrasound Obstet Gynecol. 2013; 42(1):34-40.

Nicolaides K.H, Syngelaki A., Gil M., et al. Validation of targeted sequencing of single-nucleotide polymorphisms for non-invasive prenatal detection of aneuploidy of chromosomes 13, 18, 21, X, and Y. Prenat Diagn. 2013; 33(6):575-9. Pergament E., Cuckle H., Zimmermann B., et al. Single-nucleotide polymorphism-based noninvasive prenatal screening in a high-risk and low-risk cohort. Obstet Gynecol. 2014; 124(2 Pt 1):210-8.

Policy No. MP-003-MD-DE Page 8 of 10 Dar P., Curnow K.J., Gross S.J., et al. Clinical experience and follow-up with large scale single- nucleotide polymorphism—based noninvasive prenatal aneuploidy testing. Am J Obstet Gynecol. 2014; 211: 527.

Bianchi D, Parker R, Wentworth J, et al. DNA sequencing versus standard prenatal aneuploidy screening. CARE Study Group. N Engl J Med. 2014; 370(9):799-808.

The American College of Medical Genetics and Genomics (ACMG). ACMG statement on noninvasive prenatal screening for fetal aneuploidy. Genet Med. 2013; 15(5):395-398.

Society for Maternal Fetal Medicine (SMFM). SMFM Statement: Maternal serum cell-free DNA screening in low risk women. Accessed on January 21, 2016.

Curnow KJ, Wilkins-Haug L, Ryan A, Kirkizlar E, Stosic M, Hall MP, et al. Detection of triploid, molar, and vanishing twin pregnancies by a single-nucleotide polymorphism-based noninvasive prenatal test. Am J Obstet Gynecol. 2015; 212:79.e1–79.e9.

Langlois S, Brock JA, et al. Current status in non-invasive prenatal detection of Down syndrome, trisomy 18, trisomy 13 using cell free DNA in maternal plasma. J Obstet Gynaecol Can. 2013 Feb; 35(2):177-83. Accessed on January 22, 2016.

Gregg AR, Skotko BG, Benkendorf JL, Monaghan KG, et al. Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. 2016 Oct; 18(10); 1056-1065. Accessed on May 4, 2017.

Pennsylvania Department of Human Services. Technology Assessment Group (TAG) Coverage Decisions. Managed Care Operations Memorandum: OPS # 05/2017-009. May 12, 2107. Decision: Tabled. Accessed on June 30, 2017.

American College of Obstetricians & Gynecologists (ACOG), Society for Maternal Fetal Medicine (SMFM). Screening for fetal aneuploidy. ACOG Practice bulletin No. 163. Washington, DC: ACOG; May 2016. Access on June 30, 2017.

Lalani, S.R. Cardioskeletal Muscle Disease Associated with Chromosomal Disorders. Cardioskeletal Myopathies in Children and Young Adults. 2017. Accessed on June 6, 2018.

Khandekar, S., Dive, A., Munde, P. Chromosomal abnormalities – A review. Guardian Dental College & Research Centre; January 2012. Accessed on June 7, 2018.

Policy No. MP-003-MD-DE Page 9 of 10

Policy History

Date Activity 06/07/2016 QI/UM Committee approval 12/01/2016 Provider effective date 02/09/2017 Revisions: format changes and minor grammatical changes; added Procedures #5 Genetic Counseling; Operational Guidelines update; added codes and their descriptions 03/14/2017 QI/UM Review 05/05/2017 Policy revision; Added non-coverage/experimental statement on microdeletions to Position Statement; Added several definitions in that section; Procedure Code table revised separating code 81422 as non-covered; added paragraph to Research Summary related to 81422; Additional references added to reference list. 6/30/17: policy updated to reflect ACOG’s May 2016 updates. 08/09/2017 Added Disclaimer Statement in opening of medical policy; Deleted ICD-10 code Q92.6 as ineligible code. 09/27/2017 QI/UM Committee approval 11/01/2017 Provider effective date 09/11/2018 Annual Review: Added a commercially available test to Procedures Section 1; Added and rearranged the criteria to Procedures section 2.A., 2.B., 2.K.; expanded and updated Summary of Literature; Removed ‘COVERED’ from procedure codes and diagnosis codes; expanded and added literature to Governing Bodies Approval section; added references. Removed all hyperlinks in the reference section. 09/11/2018 QI/UM Committee review Approval 11/15/2018 Provider effective date 06/25/2019 Annual Review: No clinical criteria changes; Added procedure code 0060U to the Noncovered Procedure Code table in Attachment B 07/16/2019 QI/UM Committee Review Approval 09/16/2019 Provider effective date

/KP

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